A practical guide to the interpretation of PK/PD profiles of longer-acting analogue insulins. Part one: The principles of glucose clamp studies

  • Oppel B W Greeff University of Pretoria
  • Jacob John Van Tonder Triclinium Clinical Development (Pty) Ltd
  • Kershlin Naidu University of the Witwatersrand
  • Alicia McMaster Sanofi-Aventis South Africa (Pty) Ltd
  • Alet Van Tonder Sanofi-Aventis South Africa (Pty) Ltd
  • Rashem Mothilal Sanofi-Aventis South Africa (Pty) Ltd
Keywords: analogue insulins, glucose clamp, time–action profile, glucose infusion rate, pharmacokinetics

Abstract

Glucose clamp studies are used to determine pharmacokinetics (PK) and pharmacodynamics (PD) of analogue insulins. With the development of longer-acting basal analogue insulins, including glargine 300 (Gla-300) and insulin degludec (IDeg), results from numerous glucose clamp studies are readily available. However, interpreting PK/PD profiles in a scientifically sound manner can be a challenging feat. This is the first in a series of publications that will suggest practical tips for interpreting and comparing results from glucose clamp studies. Variations in the glucose clamp methodology, duration of clamp studies and glucose clamp targets influence the study design and results significantly. Selection of study populations, including healthy patients or patients with Type 1 or 2 diabetes mellitus, has important implications. The dose of study insulin should reflect that of the general treatment population, and ideally steady-state conditions should be used. During the study the plasma insulin concentration and glucose infusion rate describe the pharmacokinetics and pharmacodynamics of the study insulin. With these practical tips in mind, results of glucose clamp studies can be interpreted in a scientifically correct manner. The next article in this series will discuss the interpretation of PK/PD profiles using two newly developed longer-acting basal analogue insulins: Gla-300 and IDeg. (Full text available online at www.medpharm.tandfonline.com/oemd) Journal of Endocrinology, Metabolism and Diabetes of South Africa 2018; DOI: 10.1080/16089677.2017.1407096

Author Biographies

Oppel B W Greeff, University of Pretoria
Department of Pharmacology University of Pretoria Pretoria
Jacob John Van Tonder, Triclinium Clinical Development (Pty) Ltd
Triclinium Clinical Development (Pty) Ltd Centurion
Kershlin Naidu, University of the Witwatersrand
Department of Internal Medicine Chris Hani Baragwanath Academic Hospital University of the Witwatersrand Johannesburg
Alicia McMaster, Sanofi-Aventis South Africa (Pty) Ltd
Sanofi-Aventis South Africa (Pty) Ltd Midrand
Alet Van Tonder, Sanofi-Aventis South Africa (Pty) Ltd
Sanofi-Aventis South Africa (Pty) Ltd Midrand
Rashem Mothilal, Sanofi-Aventis South Africa (Pty) Ltd
Sanofi-Aventis South Africa (Pty) Ltd Midrand
Published
2018-05-21
Section
Review Articles